PREECLAMPSIA IN CEREBROSPINAL FLUID ERROL NORWITZ, LAWRENCE TSEN, JOONG-SHIN PARK, PATRICIA FITZPATRICK, DAVID DORFMAN, CATALIN BUHIMSCHI, GEORGE SAADE, CHARLES LOCKWOOD, IRINA BUHIMSCHI, Yale University, Ob./Gyn. & Reprod Sci., New Haven, Connecticut, Harvard University, Obstetric Anesthesia, Boston, Massachusetts, Harvard University, Pathology, Boston, Massachusetts, University of Texas Medical Branch at Galveston, Obstetrics & Gynecology, Galveston, Texas OBJECTIVE: We previously demonstrated that proteomic analysis of cerebrospinal fluid (CSF) using SELDI-TOF mass spectrometry can accurately distinguish patients with severe preeclampsia (sPE) from both mild preeclampsia (mPE) and normotensive controls (CRL) based on the presence or absence of four discriminatory protein peaks. The current study was designed to validate these biomarkers. STUDY DESIGN: CSF was collected at the time of spinal anesthesia from women with sPE (n = 7), mPE (n = 8), and CRL (n = 7). SELDI-TOF mass spectrometry in-gel tryptic digest, on-chip immunoassays, ELISA, and spectral analysis of CSF were performed on the blinded CSF samples. RESULTS: We identified the discriminatory protein biomarkers as the glycated and non-glycated isoforms of hemoglobin aand b-chains. ELISA confirmed that levels of hemoglobin were significantly higher in the CSF of women with sPE compared with mPE and CRL (mean [95% CI]: 6.0 [3.6-8.4] vs 0.2 [-0.2-0.5] vs 0 [0-0] mg/mL; P ! .001; Figure). These levels indicate a concentration of approximately 100nM free hemoglobin in CSF of women with sPE. Direct spectrophotometry confirmed the presence of free oxyhemoglobin (414 nm max. absorbance) in CSF of women with sPE, but not in mPE or CRL. Comparisons with quantitative standards suggest that a hemoglobin equivalent of 280 lysed RBC/mL enters CSF in women with sPE. These small numbers effectively exclude a bloody tap. The changes in hemoglobin concentration are not associated with changes in CSF total protein concentration among the groups (P = .256). CONCLUSION: sPE (but not mPE) is characterized by micro-hemorrhage into CSF. These observations may have important diagnostic and/or therapeutic implications for diagnosis and management of women with preeclampsia.